Cognitive function naturally declines with age and the additional insult of adjuvant therapy may accelerate or compound this decline. Postmenopausal breast cancer comprises 75% of the disease in the U.S, yet surprisingly few have studied cognitive function in this group and few have studied cognitive function specifically related to aromatase inhibitors such as anastrozole. Five years of aromatase inhibitor therapy are prescribed for postmenopausal women with hormone receptor positive disease. However, the long term effects of this therapy on cognitive function are not known nor is it known whether cognitive function recovers after therapy ends. Finally, the impact of cognitive changes on the functional ability including the work ability of women with breast cancer has not been investigated. Preliminary analyses from our prospective study (R01CA107408) revealed significantly poorer cognitive function in postmenopausal women with early stage breast cancer (receiving anastrozole with or without chemotherapy) compared to healthy postmenopausal women and cognitive function deteriorated in these breast cancer cohorts up to 18 months post-anastrozole initiation suggesting that cognitive function continues to deteriorate with longer duration of therapy. Women with breast cancer also experienced deteriorating functional ability over time. These compelling findings of continued cognitive decline after 18 months of anastrozole underscore the need to logically extend this work to determine the long term cognitive effects of this therapy. We are uniquely positioned to capitalize on our existing cohorts of women with breast cancer and healthy controls and our pretreatment cognitive assessments to launch this competitive renewal to determine the long term trajectory of cognitive function through the remaining years of anastrozole therapy and whether cognitive function recovers after therapy ends. We will also determine factors that influence risk for cognitive decline with therapy and how changes in cognitive function impact women's functional ability particularly their work ability. The specific aims of this proposed longitudinal study are to: 1) Determine the long term (yearly assessments during the remaining treatment period) effect of anastrozole therapy on cognitive function in postmenopausal women with early stage breast cancer, 2) Determine whether cognitive function recovers at 1 year after the conclusion of anastrozole relative to the level of cognitive function at the last assessment while on anastrozole therapy in women with breast cancer who received anastrozole with or without chemotherapy, 3) Explore the factors that are related to deterioration in cognitive function with anastrozole therapy and to the recovery of cognitive function 1 year after the conclusion of therapy in women with breast cancer who receive anastrozole with or without chemotherapy and 4) Explore the impact of changes in cognitive function related to anastrozole therapy on functional ability in women with breast cancer. PUBLIC HEALTH RELEVANCE: Results from our ongoing study of cognitive function (i.e., attention, memory) with the hormonal agent, anastrozole (Arimidex), for breast cancer reveal continued decline in cognitive function after 18 months of therapy. This proposed study will complete the picture of the effects of anastrozole on cognitive function in women with breast cancer by determining the long term trajectory of cognitive function through the remaining years of therapy and whether cognitive function recovers after therapy ends. The study will also identify factors that influence risk for cognitive decline with therapy and how changes in cognitive function impact women's functional ability particularly their work ability.